¹University of Alabama at Birmingham: Department of Surgery, Division of Neurosurgery, San Diego, CA, USA

²Georgetown University Medical Center: Department of Neurosurgery, San Diego, CA, USA

³University of Alabama at Birmingham: Department of Microbiology, San Diego, CA, USA

⁴University of Alabama at Birmingham: Department of Pathology, Division of Neuropathology, San Diego, CA, USA

⁵Georgetown University Medical Center: Department of Neurology, San Diego, CA, USA

⁶University of British Columbia Departments of Microbiology and Immunology, and Neurovir Therapeutics, Inc, San Diego, CA, USA

Correspondence to: M D Medlock, Georgetown University Neurosurgery, Pasquerilla One, 3800 Reservoir Road NW, Washington, DC 20007, USA

G207 is a conditionally replicating derivative of herpes simplex virus (HSV) type-1 strain F engineered with deletions of both ₁34.5 loci and a lacZ insertion disabling the U_L39 gene. We have demonstrated the efficacy of G207 in treating malignant glial tumors in athymic mice, as well as the safety of intracerebral G207 inoculation in mice and in Aotus nancymai. We sought to determine the safety of G207 inoculation into cerebral malignant glial tumors in humans. Criteria for inclusion into this dose-escalation study were the diagnosis of histologically proven malignant glioma, Karnofsky score 70, recurrence despite surgery and radiation therapy, and an enhancing lesion greater than 1 cm in diameter. Serial magnetic resonance images were obtained for volumetric analysis. The trial commenced at a dose of 10⁶ plaque forming units (p.f.u.) inoculated at a single enhancing site and was completed when the 21st patient was inoculated with 3 ´ 10⁹ p.f.u. at five sites. While adverse events were noted in some patients, no toxicity or serious adverse events could unequivocally be ascribed to G207. No patient developed HSV encephalitis. We found radiographic and neuropathologic evidence suggestive of anti-tumor activity and long-term presence of viral DNA in some cases. Gene Therapy (2000) 7, 867-874.

HSV; glioblastoma; anaplastic astrocytoma; human; gene therapy